Repairing bone defects and augmentation of existing bone often require the use of bio-resorbable materials, which may include autogenous bone graft, allogeneic bone graft, or alloplastic materials. Synthetic bone graft materials are alternatives to autogenous and allogenic bone, and these include calcium phosphates, calcium sulfate, hydroxyapatite, resorbable polymers, bioglass, and various combinations of bone derivatives. Calcium sulfate has been used for many years in dentistry and medicine. In its hemihydrate form, calcium sulfate has been used as a bone graft material and is known as a biocompatible, completely biogradable, and safe material. It has further been demonstrated in animal and clinical studies to have osteoconductive stimulation property that can be used for bone augmentation and improving the repair of bone defects.
Previous research of the present inventors has shown that calcium sulfate causes precipitation of calcium phosphate deposits as it dissolves at the surgical site. These precipitates stimulate and direct the formation of new bone. Moreover, to achieve optimal result, it is desirable that calcium sulfate, calcium phosphate, or any other bone repair materials stay at the surgical site for a considerable period of time, in order to inhibit soft tissue filling of the defect and to effectively stimulate bone growth.
However, when conventional calcium sulfate is used as a cement to fill a bone void, fracture, or other defects in human bone, this material dissolves at a rapid rate, with a complete dissolution in about four weeks, and cannot be retained at the site for longer periods. As such, the principal concern and deficiency with the conventional calcium sulfate are that calcium sulfate dissolves too rapidly at a recipient site, this outpaces the formation of new bone in human patients. Therefore, a need arises for improved calcium sulfate material which degrades at the recipient site in a rate desirably matching the rate of bone growth.
Recently, Ricci et al (U.S. Pat. No. 6,770,695 B2) disclose polymer containing calcium sulfate particles that comprise resorbable polymers mixed with or coated on calcium sulfate. The resorbable polymers slow down dissolution of the particles in the recipient site and improve the effect of the grafting material in bone augmentation and repairing. However, polymers are more expensive, which increases the cost of the implant material. Moreover, polymers, such as commonly used polylactic acid and polyaspirin, could have negative effect on bone formation. Polylactic acid releases acidic degradation products which could potentially lead to bone resorption rather than bone formation, especially when used in high quantities. Polyaspirin releases salicylic acid as a result of its degradation, which may also potentially lead to bone resorption when used in high quantities.
On the other hand, Park et al (U.S. Pat. No. 7,767,226) recently disclose hemihydrate calcium sulfate nanoparticles and method of use in facilitating bone repair. Park et al disclose various known methods for producing calcium sulfate nanoparticles. More specifically, microemulsion technique for making calcium sulfate dihydrate nanoparticles has been described by Rees, et al. (Langmuir 15 (1999) 1993-2002). Another method is cryo-vacuum technique described Salvadori, et al. (Journal of Colloid and Interface Science, 2005, 1-4). This technique involves quick freezing a solution of conventional calcium sulfate and dehydrating the frozen ice of the solution of calcium sulfate under vacuum (lyophilization). Moreover, in order to form hemihydrate nanoparticles, the freeze-dried crystals can be heated and dried in an oven to obtain β-form calcium sulfate hemihydrate nanoparticles. α-form calcium sulfate hemihydrate nanoparticles can be obtained by autoclaving the calcium sulfate dihydrate nanoparticles.
Park et al further disclose compositions comprising hemihydrate calcium sulfate nanoparticles and a growth factor, such as PDGF, IGF-I, TGF-β and others. As demonstrated by the release of PDGF, Park et al disclose that calcium sulfate nanoparticles degrade faster than conventional calcium sulfate. This is thought to be beneficial for rapid release of the growth factor. However, as discussed above, faster dissolution of calcium sulfate nanoparticles is undesirable, because it outpaces the formation of new bone.
Therefore, there is a need for improved calcium sulfate particles and bone grafting materials for repairing bone defects and augmentation of existing bone.